Malignant Hyperthermia (MH) is an autosomal dominant disorder of skeletal muscle that causes a life threatening reaction following administration of commonly used inhalational anesthetics such as halothane, or the depolarizing muscle relaxant succinylcholine. Administration of the anesthetics during surgery causes an altered release of calcium from the sarcoplasmic reticulum (SR) through the ryanodine receptor (RYR1), which in turn induces a cascade of biochemical events that culminates in a nypermetabolic state (fulminant episode) with hyperthermia. If not treated, promptly by withdrawing the anesthetic and administering dantrolene (a drug that inhibits release of Ca++ from the SR) mortality can be as great as 70%. Because most MH individuals appear normal and susceptibility becomes apparent only after exposure to anesthetics, identifying MH susceptible individuals prior to surgery is difficult requiring muscle biopsy and measurements of the contractile sensitivity to RYR1 agonists caffeine and halothane. The caffeine-halothane contracture test (CHCT) phenotypes patients as MHS (susceptible) or MHN (normal). The CHCT has a sensitivity of 93% and specificity of 78%. USUHS has performed over 400 CHCT tests on patients. Approximately 50% of patients are diagnosed CHCT positive. Core C will review MH susceptible individuals, probands and family members for clinical histories of adverse responses to anesthetic drugs, phenotype skeletal muscle samples with performance of a CHCT, and genotype CHCT positive patients for causative mutations in RyR1 and the a1s-DHPR genes. They will collect blood samples from these patients a) for mRNA for use in profiling studies, b) to make permanent B-lymphocyte cell lines for physiologic and transcriptional profiling studies, and c) for the isolation of dendritic cells. In addition, they will collect muscle samples to make myoblast cultures to be purified by Core B, and flash freeze discarded muscle samples for transcriptional profiling studies.